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脂质代谢的谱系特异性差异及其对结核分枝杆菌临床株的影响。

Lineage-specific differences in lipid metabolism and its impact on clinical strains of Mycobacterium tuberculosis.

机构信息

School of Life Sciences, College of Agriculture, Engineering and Science, University of KwaZulu-Natal, South Africa.

出版信息

Microb Pathog. 2020 Sep;146:104250. doi: 10.1016/j.micpath.2020.104250. Epub 2020 May 11.

Abstract

Mycobacterium tuberculosis (M. tb) is the causative agent of TB and its incidences has been on the rise since 1993. Lipid metabolism is an imperative metabolic process, which grants M. tb the ability to utilize host-derived lipids as a secondary source of nutrition during infection. In addition to degrading host lipids, M. tb is proficient at using lipids, such as cholesterol, to facilitate its entry into macrophages. Mycolic acids, constituents of the mycobacterial cell wall, offer protection and aid in persistence of the bacterium. These are effectively synthesized using a complex fatty acid synthase system. Many pathogenesis studies have reported differences in lipid-metabolism of clinical strains of M. tb that belongs to diverse lineages of the Mycobacterium tuberculosis complex (MTBC). East-Asian and Euro-American lineages possess "unique" cell wall-associated lipids compared to the less transmissible Ethiopian lineage, which may offer these lineages a competitive advantage. Therefore, it is crucial to comprehend the complexities among the MTBC lineages with lipid metabolism and their impact on virulence, transmissibility and pathogenesis. Thus, this review provides an insight into lipid metabolism in various lineages of the MTBC and their impact on virulence and persistence during infection, as this may provide critical insight into developing novel therapeutics to combat TB.

摘要

结核分枝杆菌(M. tb)是结核病的病原体,自 1993 年以来,其发病率一直在上升。脂代谢是一种必要的代谢过程,使 M. tb 能够在感染期间利用宿主来源的脂质作为营养的次要来源。除了降解宿主脂质外,M. tb 还擅长利用胆固醇等脂质来促进其进入巨噬细胞。分枝杆菌细胞壁的组成部分——分枝菌酸,提供保护并有助于细菌的持续存在。这些物质是通过复杂的脂肪酸合成系统有效地合成的。许多发病机制研究报告称,属于结核分枝杆菌复合群(MTBC)不同谱系的 M. tb 临床菌株的脂代谢存在差异。与传播性较低的埃塞俄比亚谱系相比,东亚和欧美谱系具有“独特的”细胞壁相关脂质,这可能使这些谱系具有竞争优势。因此,了解 MTBC 谱系之间的脂代谢及其对毒力、传染性和发病机制的影响至关重要。因此,本综述深入探讨了 MTBC 不同谱系中的脂代谢及其对感染期间毒力和持续存在的影响,这可能为开发新型治疗结核病的药物提供重要的见解。

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